In this study we describe by use of accelerometers the total physical activity (PA), intensity pattern and walking capacity in 87 persons age 16-45 years with Down syndrome (DS), Williams syndrome (WS) and Prader-Willi syndrome (PWS). Participants were recruited from all over Norway, and lived either with their parents or in community residences with support. On average the participants generated 294 counts per minute (cpm) or 6712 steps per day, with most of the day spent in sedentary activity, 522 min/day, followed by 212 min/day in light PA, 71 min/day in lifestyle activity and 27 min/day in moderate-to-vigorous physical activity (MVPA). Inactivity was prevalent, as only 12% meet the current Nordic recommendations for PA. When compared, no differences for total physical activity or time in MVPA were observed between the three groups. However, participant with DS spent a mean of 73 min/day less and 43 min/day less in sedentary activities compared to participants with PWS and WS, respectively, (p=0.011, 95% CI: -10.9; -80.1). In addition the DS-group spent a mean of 66 min/day more in light PA than the PWS-group and 41 min/day more than the WS-group, (p<0.001, 95% CI: 29.3; 79.7). Participants with PWS spent on average 30 min/day less in lifestyle activities compared to both participants with DS and WS, (p<0.001, 95% CI: -14.2; -45.4). No association between total PA and BMI were observed. Males were more active than females across all diagnoses. Males accumulated on average 85 counts per minutes more than females, (p=0.002, 95% CI: 33.3; 136.7), 2137 more steps per day, (p=0.002, 95% CI: 778; 3496). The mean walking capacity during six-minutes was 507 m (SD 112 m) for males and 466 m (SD 88 m) for females. Distance walked during testing decreased with 33.6 m when comparing normal or underweight participants to overweight participants, and 78.1 m when comparing overweight to obese participants (p<0.001 95% CI: -40.4; -85.8). When adjusted for BMI no differences in walking capacity between the three genetic conditions were observed.

ABSTRACT.Purpose: To study ocular characteristics in 87 patients with verified Marfan syndrome (MFS) based on the Ghent criteria from 1996 (Ghent-1). Methods: The position of the lens was noted by observing the eye in different gaze directions in maximal mydriasis during slit lamp examination. Ectopia lentis (EL) was classified as subluxated (dislocation slightly backwards) or luxated (vertical or horizontal displacement). Corneal curvature, axial length (AL), corneal diameter, central corneal thickness, anterior chamber depth, lens thickness, condition of the iris, intraocular pressure, spherical equivalent and visual acuity were also investigated. Results: EL was found in 108 eyes (62.1%). Of the 68 phakic eyes with EL, 43 (63.2%) had subluxation. Mean AL was 24.80 AE 2.57 mm, and the AL was above 23.5 mm in 65.3%. Mean keratometry (K) in phakic eyes was 41.79 AE 1.70 diopters (D), and the K value was <41.5D in 46.8%. Iris hypoplasia was found in 3.4%. Myopia above 3D occurred in 38.4% of the phakic eyes. Mean binocular logMAR was 0.10 AE 0.32. Only five patients (5.7%) had a logMAR more than 0.5. These 5 patients had EL, and 4 of them were amblyopic. Conclusion: In this strictly defined MFS group fulfilling the Ghent-1 criteria, the prevalence of EL was 62.1%. In many cases, the dislocation of the lens was subtle. On average, the corneas were flattened and the globe length was increased. Only a few patients were visually impaired. Children with MFS should have a thorough follow up to avoid amblyopia.

No abstract

In monogenic disorders, correlation between genotype and phenotype is a premise for predicting prognosis in affected patients. Predictive genetic testing may enable prophylaxis and promote clinical follow-up. Although Marfan syndrome (MFS) is known as a monogenic disorder, according to the present diagnostic criteria a mutation in the gene FBN1 is not sufficient for the diagnosis, which also depends on the presence of a number of clinical, radiological, and other findings. The fact that MFS patient cohorts only infrequently have been examined for all relevant phenotypic manifestations may have contributed to inconsistent reports of genotype-phenotype correlations. In the Norwegian Study of Marfan syndrome, all participants were examined for all findings contained in the Ghent nosology by the same investigators. Mutation identification was carried out by robot-assisted direct sequencing of the entire FBN1 coding sequence and MLPA analysis. A total of 46 mutations were identified in 44 unrelated patients, all fulfilling Ghent criteria. Although no statistically significant correlation could be obtained, the data indicate associations between missense or splice site mutations and ocular manifestations. While mutations in TGF-domains were associated with the fulfillment of few major criteria, severe affection was indicated in two cases with C-terminal mutations. Intrafamilial phenotypic variation among carriers of the same mutation, suggesting the influence of epigenetic facors, complicates genetic counseling. The usefulness of predictive genetic testing in FBN1 mutations requires further investigation.